Project summary Breast cancer is the most common cancer in women, with over two-hundred and sixty thousand new cases expected in the United States in 2018 alone. There are estimated to be more than 3 million breast cancer survivors in the US due to substantial advances in detection and treatment, with this number continuing to grow. However, treatments also increase risk for long-term and late toxicities, including effects on physical and cognitive function that interfere with quality of life. One possible explanation recently proposed is that the toxicity of cancer treatments may directly accelerate the aging process in some patients, leading to earlier onset of age-related symptoms such as cognitive complaints, fatigue, declines in physical function, and lasting pain. However, this hypothesis has not been rigorously tested in clinical populations. Our study will examine the effects of common breast cancer treatments as they relate to markers of biological aging, inflammation, and reports of physical and cognitive complaints in a prospective study of breast cancer patients assessed prior to and after exposure to chemotherapy and/or radiotherapy. The proposed study will leverage an existing NCI- funded cohort of women with early-stage breast cancer assessed before onset of adjuvant therapy with radiation (RT), chemotherapy (CT), or endocrine therapy and again after completion of RT and/or CT and at follow-up visits occurring 6-, 12-, and 18-month post-treatment, with serial blood specimens for plasma, DNA and RNA analyses. In this well characterized cohort of breast cancer survivors, we propose to add the assessment of markers of biological aging using existing collected specimens and add a new behavioral assessment at 7 years post treatment to 1) examine the effects of breast cancer treatments on the biological aging process, 2) test the relationship between accelerated biological aging and cognitive and physical complaints in breast cancer patients over the follow-up period, and 3) test whether inflammatory factors mediate the relationship between biological aging and cognitive and physical complaints.